Stabilized formulations containing anti-PCSK9 antibodies

Patent metadata

Field	Value
Publication number	US-10472425-B2
Application number	US-201715603732-A
Country	US
Kind code	B2
Filing date	May 24, 2017
Priority date	Jul 28, 2011
Publication date	Nov 12, 2019
Grant date	Nov 12, 2019

Abstract

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human proprotein convertase subtilisin/kexin type 9 (PCSK9). The formulations may contain, in addition to an anti-PCSK9 antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.

First claim

What is claimed is:

1. A liquid pharmaceutical formulation consisting of:
(a) 50±7.5 mg/mL to 250±37.5 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;
(b) 5±0.75 mM to 10±1.5 mM histidine, pH 6.0±0.3;
(c) 0.01±0.0015% w/v polysorbate 20; and
(d) 10±1.5% w/v sucrose;
in water.

2. The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises 50 mg/mL of the antibody or antigen-binding fragment thereof.

3. The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises 75 mg/mL of the antibody or antigen-binding fragment thereof.

4. The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises 100 mg/mL of the antibody or antigen-binding fragment thereof.

5. The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises 150 mg/mL of the antibody or antigen-binding fragment thereof.

6. The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises 175 mg/mL of the antibody or antigen-binding fragment thereof.

7. A liquid pharmaceutical formulation consisting of:
(a) 75 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;
(b) 8±1.2 mM histidine, pH 6.0±0.3;
(c) 0.01±0.0015% w/v polysorbate 20; and
(d) 10±1.5% w/v sucrose;
in water.

8. A liquid pharmaceutical formulation consisting of:
(a) 150 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;
(b) 6±0.9 mM histidine (pH 6.0±0.3);
(c) 0.01±0.0015% w/v polysorbate 20; and
(d) 10±1.5% w/v sucrose;
in water.

Assignees

• Regeneron Pharma

Inventors

• Walsh Scott M
• Dix Daniel B

Classifications

• A61M5/31513

  Piston constructions to improve sealing or sliding · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61M5/3202

  Devices for protection of the needle before use, e.g. caps (A61M5/50 takes precedence; for infusion spikes A61M5/1626; protectors for sharps A61B50/3001) · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K39/39591

  Stabilisation, fragmentation · CPC title